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Regular physical activity as a circadian Zeitgeber
Fenclová, Aneta ; Bendová, Zdeňka (advisor) ; Červená, Kateřina (referee)
The function of almost every cell in the body is regulated by the circadian system. At the whole-body level, this system consists of the main oscillator, which is formed by the suprachiasmatic nucleus of the hypothalamus, and peripheral oscillators of individual organs and tissues. This system is sensitive to periodic changes in the external environment, particularly to the alternation of light and darkness, and under unfavorable lighting conditions, it can lead to desynchronization of both this timing system with the solar cycle and the mutual desynchronization of individual organs and tissues. This temporal mismatch of physiological processes can cause a range of diseases and metabolic disorders, and can be partially prevented by regular physical activity. Daily oscillations of circadian rhythms in many cardiovascular and metabolic parameters also determine the ideal time of day for anaerobic performance. This bachelor's thesis is a selection and comparison of information from professional literature and available studies dealing with the mutual influence of physical activity and circadian rhythms. There are works mentioned here that test the effect of physical activity on internal desynchronization of the melatonin rhythm and sleep pattern, on the circadian synchronization of skeletal muscle, as...
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Pathogenesis of nephrotic syndrome in children and predictors of corticosteroid treatment response
Bezdíčka, Martin ; Souček, Ondřej (advisor) ; Doležel, Zdeněk (referee) ; Reiterová, Jana (referee)
Nephrotic syndrome is a kidney disease caused by injury of the podocytes. It can be secondary due to infection, systemic disease or certain drugs, but it may also present as sudden primary nephrotic syndrome without obvious inducer. Current standard treatment has many severe adverse effects. In some patients that are resistant to the initial several-week-long glucocorticoid treatment it is possible to reveal the causative genetic aetiology of the disease, whereas in the rest of them aetiology remains unknown. Those who respond well to initial glucocorticoid treatment and achieve remission may later on develop repeated relapses requiring long-term glucocorticoid therapy. This work describes our original research studies focusing on the improvement of genetic diagnostics of nephrotic syndrome, on the exploration of molecular mechanisms of the second most common genetic cause of the steroid-resistant nephrotic syndrome (transcription factor WT1 mutants) and on the search of clinical and laboratory factors that could predict the resistence to glucocorticoid treatment. By combining Sanger and next-generation sequencing (NGS) we were the first to identify monogenic cause in 38 % of Czech and Slovak children with steroid-resistant nephrotic syndrome whose samples had been collected for 18 years. The most...
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Effect of stress on corticosteroid metabolism in peripheral tissues
Makal, Jakub ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
Stressor influence can lead to homeostatic disruption. To eliminate this threat, mechanism which compensates negative effects of stressor was evolved by organisms. It's called stress response. One of two major systems that moderate stress response of organism is hypothalamic- pituitary-adrenal axis (HPA axis). Effectors of the HPA axis are glucocorticoids, steroid hormones secreted from adrenal glands. Enzymes which metabolize glucocorticoids are located in target tissues for these hormones. They convert active glucocorticoids into their inactive forms, or vice versa. Untill now, two such enzymes have been described - 11beta-hydroxysteroid dehydrogenases type 1 and type 2. It was proved that expression and activity of these enzymes can change under the influence of stressor. These changes are tissue-specific and dependent on type of applied stressor.
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Effect of stress on expression of 11β-hydroxysteroid dehydrogenase in rat brain
Kuželová, Andrea ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
This thesis examines the influence of stress on the activity of hippocampal CA1 area. The main task was to determine whether the stress load affects the changes of the local metabolism of glucocorticoids, and whether the levels of corticosteroid receptors in the CA1 hippocampus are modulated in response to stress. In order to answer these questions, the experiments were carried out using three different rat strains - Fisher, Lewis and Wistar which differ in their activities of hypothalamic-pituitary-adrenal axis. Our results demonstrate that stress has no effect on expression of MR mRNA. Conversely, stress reduces the levels of GR mRNA in CA1 area of the dorsal hippocampus. Moreover, we confirmed that the Lewis and Wistar rats didn't change metabolism of glucocorticoids after stress response. By the Fisher rats increased levels of 11β-HSD1 mRNA expression and therefore increased the metabolism of corticosterone.
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Impact of glucocorticoid treatment on musculosceletal system of pediatric patients with acute lymphoblastic leukemia.
Petráčková, Karolína ; Jevič, Filip (advisor) ; Šrámková, Lucie (referee)
This bachelor thesis aims to provide a general overview of complications of musculoskeletal system in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) undergoing chemotherapy treatment involving high cumulative doses of glucocorticoids. Musculoskeletal complications include steroid myopathy, osteonecrosis and reduced bone mineral density. The first part describes their basic pathophysiological mechanisms and the risk factors of their origin. The second part presents the current possibilities of muscle strength assessment and available exercise programs. Furthermore, diagnosis of osteonecrosis and bone mineral density are presented together with current possibilities of therapeutic intervention. The thesis also covers characteristics of muscle strength measuring methods and exercise programs along with presentation of the results of individual studies. In the discussion part, there are broken down the limits, advantages and disadvantages of using the muscle strength measuring methods and exercise programs in clinical practice.
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Noninvasive measurement of steroid homones and effect of hormonal manipulation on behaviour in the gecko Paroedura picta
Matušková, Lucie ; Kratochvíl, Lukáš (advisor) ; Fraňková, Marcela (referee)
Hormones influence life of all animals. Not only they affect physiological changes in organisms, but also impact their behaviour. This work focuses at two main groups of steroid hormones: glucocorticoids and androgens. Glucocortiods are activated in response to stress. Their levels can be measured using non-invasive methods, which have a range of advantages. The main advantage is the feedback-free sample collection for enzyme immunoassay. As the measurement involves metabolites of the hormones rather than the hormones themselves, prior validation of the method is, however, necessary. This work reports on a study aiming to validate non-invasive measurement on the Madagascar Ground Gecko (Paroedura Picta). The validation was based on ACTH challenge test: Synacthen Depot was injected, which should lead to increased blood level of glucocorticoids. The validation, however, was not successful. The measurement did not discover significant increase in the levels of the metabolites of glucocorticoids. In addition, the work focuses on behavioural effects of testosterone, the primary androgen. Hormonal manipulations have been carried out on several male and female specimens. The results have discovered differences in sexual behaviour between control groups. On the other hand, the hormonal manipulations had no...
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The influence of pulse glucocorticoid therapy on ECG
Juríková, Nikola ; Vlček, Jiří (advisor) ; Rozsívalová, Petra (referee)
Candidate: Nikola Juríková1 Supervisor: prof. RNDr. Jiří Vlček, CSc.1 Consultant: doc. MUDr. Tomáš Soukup, PhD.2 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University 2 2nd Department of Internal Medicine - Gastroenterology, University Hospital in Hradec Králové Title of the master thesis: Effect of pulse glucocorticoid therapy on ECG Glucocorticoid pulse therapy (PT) is used to terminate acute exacerbations of immunologically mediated diseases. The aim of this thesis was to analyze the influence of methylprednisolone (MP) PT on ECG changes, mainly on QT interval, as prolonged QT interval may induce ventricular arrhythmias and to identify other risk factors (RF) for QT prolongation. Data were gained retrospectively from medical records of patients hospitalized at II. Internal Gastroenterology Clinic of University Hospital Hradec Králové. QT was corrected to QTc using Bazzet (QTcB) and Fridericia (QTcF) formula, QTc >450 ms (men) and QTc >460 ms (women) was considered prolonged. QTc changes before and after pulse therapy were determined as ∆QTc. 325 pulses of MP were administered to 277 patients (66,0 % women), ECG was available in 94,2 % (n=306 from 325). After PT there was significant ∆QTcF 14,6 ms (p <0,001) and ∆QTcB 5,6 ms (p <0,001)....
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Influence of corticosteroids and movement disorder on development of osteoporosis in patients with multiple sclerosis (MS)
Týblová, Michaela ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Taláb, Radomír (referee)
Introduction: Multiple sclerosis (MS) is associated with impaired bone health in comparison to an equally healthy population, even already in patients at the onset of this disease. The main risk factors for development of osteoporosis in MS patients are known. The aim of the study was to find the relationship of the decrease in bone mineral density (BMD) to the administered cumulative dose of steroids and to other risk factors in MS, mainly to the degree of motor deficit. Further goal was to evaluate the occurence of the risk of low-trauma fractures in multiple sclerosis patients.. The BMD and muscle mass was compared in MS patients (women and men) and control subjects, to examine the effect of main ones - physical disability and long-term glucocorticoid (GC) therapy on BMD. Clinical values of bone remodeling markers were evaluated in assessment of rate of bone loss in patients with multiple sclerosis long term treated with low dose of GC. Patients and methods: We used dual -energy X-ray absorptiometry for a measurement of BMD in 591 MS patients (455 females and 136 males) in 2004 and in cross-sectional longitudinal study published in 2014 with 474 patients (353 women and 121 men). Out of the whole study group body composition was evaluated in 250 MS females, 104 males and 247 healthy controls (193...
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The influence of pulse glucocorticoid therapy on ECG
Bosaková, Nikola ; Vlček, Jiří (advisor) ; Rozsívalová, Petra (referee)
Candidate: Nikola Juríková1 Supervisor: prof. RNDr. Jiří Vlček, CSc.1 Consultant: doc. MUDr. Tomáš Soukup, PhD.2 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University 2 2nd Department of Internal Medicine - Gastroenterology, University Hospital in Hradec Králové Title of the master thesis: Effect of pulse glucocorticoid therapy on ECG Glucocorticoid pulse therapy (PT) is used to terminate acute exacerbations of immunologically mediated diseases. The aim of this thesis was to analyze the influence of methylprednisolone (MP) PT on ECG changes, mainly on QT interval, as prolonged QT interval may induce ventricular arrhythmias and to identify other risk factors (RF) for QT prolongation. Data were gained retrospectively from medical records of patients hospitalized at II. Internal Gastroenterology Clinic of University Hospital Hradec Králové. QT was corrected to QTc using Bazzet (QTcB) and Fridericia (QTcF) formula, QTc >450 ms (men) and QTc >460 ms (women) was considered prolonged. QTc changes before and after pulse therapy were determined as ∆QTc. 325 pulses of MP were administered to 277 patients (66,0 % women), ECG was available in 94,2 % (n=306 from 325). After PT there was significant ∆QTcF 14,6 ms (p <0,001) and ∆QTcB 5,6 ms (p <0,001)....
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Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
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